Pancreatic polypeptide (PP) occurs in multiple molecular forms. It has been found that extracts of cultured endocrine cells contain immunoreactive PP-like peptides different in both size and charge from PP itself. When the extracts were fractionated by sodium dodecyl sulfate polyacrylamide gel electrophoresis or guanidine hydrochloride column chromatography a small relative proportion of the total immunoreactivity migrated or eluted in positions corresponding to a peptide about 7500 molecular weight. The bulk of the immunoreactivity corresponds closely in apparent molecular weight to PP itself (4200 d.) but differs in charge when analyzed by isoelectric focusing. These observations raise the question whether it is PP or a molecule closely related to PP that is actually the endocrine product of the pancreatic PP-producing cell. We propose to elucidate the structural basis for the differences in the immunoreactive PP-like culture products, to investigate the efficiency of extraction of these peptides from pancreas tissue, to determine their relative amounts in extracts of intact pancreas, to determine biosynthetic relationships existing among these peptides and to prepare sufficient quantities for complete structural analysis and biological testing.